High Calcium Crystalloid Therapy for Cardiac Arrest

(SPEAR Trial)

Overseen By Cara Spivy, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Carol Bernier

Must not be taking: Digitalis

Disqualifiers: Under 18, Pregnancy, DNR, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 1 hour

342 Participants Needed

Trial Summary

What is the purpose of this trial?

The Carilion Clinic and Virginia Tech Carilion School of Medicine, in conjunction with Roanoke Fire-EMS, Botetourt County Department of Fire \& EMS and Salem Fire-EMS, are studying the outcomes of patients experiencing Pulseless Electrical Activity (PEA). PEA refers to a type of cardiac arrest in which there is normal electrical activity in the heart however the heart still fails to contract to generate a pulse. Without heart contractions, which normally generates a pulse, the brain and other important organs fail to receive blood and oxygen. Unfortunately, the majority (97.3%) of patients that experience this rhythm do not survive and most don't even make it to the hospital. This study is trying to determine if the administration of a High Calcium, Low Sodium (HCLS) fluid in pre-hospital care will improve the chances of survival. Generally, a sodium (salt) solution is provided to patients experiencing cardiac arrest. Studies have shown that lower sodium and higher calcium content may activate certain parts of the heart cells required to generate a pulse under PEA conditions. This study is a double-blind, prospective, clinical trial. PEA patients will randomly receive either routine fluid therapy (salt solution) or a HCLS solution. While HCLS solution is not the standard fluid used by EMS providers responding to PEA, it is composed of FDA approved components and is occasionally used by EMS providers at their discretion in treating PEA. It is predicted that HCLS will either improve PEA survival or deliver similar outcomes as routine treatment. All patients will receive standard, high quality cardiac arrest and post-cardiac arrest care regardless of assigned treatment group.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

Is High Calcium Crystalloid Therapy safe for humans?

High levels of calcium can be harmful to the heart, potentially causing irregular heartbeats or cardiac arrest. Studies have shown that using calcium during cardiac arrest does not improve survival rates, and there are reports of dangerously high calcium levels in the blood after treatment. ^{1 2 3 4 5}

How is High Calcium, Low Sodium Crystalloid Therapy different from other treatments for cardiac arrest?

High Calcium, Low Sodium Crystalloid Therapy is unique because it focuses on using a solution with high calcium and low sodium levels, which is different from standard treatments that do not typically adjust these specific electrolyte levels. This approach is novel as it aims to enhance myocardial protection during cardiac arrest, although the effectiveness of calcium in improving survival rates during cardiac arrest is still unclear based on existing studies. ^{1 3 5 6 7}

What data supports the effectiveness of the treatment High Calcium, Low Sodium Crystalloid Therapy for cardiac arrest?

There is no evidence that administering calcium during cardiopulmonary resuscitation improves survival from cardiac arrest. Calcium has been used in specific conditions like hyperkalemia (high potassium levels) and hypocalcemia (low calcium levels), but its role in cardiac arrest remains unclear due to limited evidence. ^{1 5 7 8 9}

Research Team

Carol Bernier, DO

Principal Investigator

Virginia Polytechnic Institute and State University

Eligibility Criteria

The SPEAR study is for patients who experience a type of cardiac arrest called PEA, where the heart's electrical activity is normal but it doesn't contract. Participants must be treated by certain EMS providers in Roanoke and not have a DNR order, known pregnancy, untreated cardiac arrest over 30 minutes, traumatic cardiac arrest, LVAD device or digitalis toxicity.

Inclusion Criteria

I was unconscious and had no pulse but my heart wasn't in a common irregular rhythm.

Exclusion Criteria

I may have side effects from heart medication.

I experienced a heart stoppage for over 30 minutes without treatment.

I have a DNR order and do not wish to be enrolled in the trial.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Immediate

Treatment

Patients receive either routine fluid therapy (normal saline) or a High Calcium, Low Sodium (HCLS) solution during pre-hospital care

Up to 1 hour

Follow-up

Participants are monitored for neurological outcomes and survival to hospital discharge

Up to 30 days

Treatment Details

Interventions

• High Calcium, Low Sodium (HCLS) Crystalloid Therapy

Trial Overview This trial tests if High Calcium, Low Sodium (HCLS) fluid improves survival in PEA compared to standard salt solution therapy. It's a double-blind study meaning neither the patient nor provider knows which treatment is given. Patients are randomly assigned to receive either HCLS or routine fluid therapy.

Participant Groups

Group I: High-Calcium, Low- Sodium (HCLS) group Experimental Treatment 1 Intervention

Patients will receive a drip of blinded, intravenous, half-normal saline and an unblinded, intravenous, one gram bolus of calcium chloride.

Group II: High-Calcium, High- Sodium (HCHS) group Active Control 1 Intervention

Patients will receive a drip of blinded, intravenous, normal saline and an unblinded, intravenous, one gram bolus of calcium chloride.

High Calcium, Low Sodium (HCLS) Crystalloid Therapy is already approved in United States for the following indications:

Approved in United States as High Calcium, Low Sodium Crystalloid Therapy for:

• Pulseless Electrical Activity (PEA) in cardiac arrest

Who Is Running the Clinical Trial?

Carol Bernier

Lead Sponsor

Trials

1

Recruited

340+

Virginia Polytechnic Institute and State University

Collaborator

Trials

162

Recruited

26,900+

Findings from Research

A review of 48 studies found that administering calcium during cardiopulmonary resuscitation (CPR) does not improve survival rates from cardiac arrest, regardless of the heart's rhythm.

The role of calcium in specific conditions like hyperkalemia or calcium channel blocker intoxication remains uncertain due to limited evidence, highlighting a significant gap in research on this topic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcium administration during cardiac arrest: a systematic review. Kette, F., Ghuman, J., Parr, M.[2018]

In the COCA trial involving 391 patients with out-of-hospital cardiac arrest, calcium administration after adrenaline did not improve survival rates compared to placebo, with only 4.7% of patients in the calcium group alive at 1 year versus 9.1% in the placebo group.

The study also found that fewer patients in the calcium group had a favorable neurological outcome (3.6%) compared to the placebo group (8.6%), indicating that calcium may be harmful rather than beneficial in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of calcium vs. placebo on long-term outcomes in patients with out-of-hospital cardiac arrest. Vallentin, MF., Granfeldt, A., Meilandt, C., et al.[2022]

Calcium chloride has been historically used for resuscitating patients in asystole and electromechanical dissociation (EMD), but recent studies, including a randomized controlled trial, show no significant improvement in resuscitation rates or long-term survival compared to saline.

While calcium chloride may improve resuscitation rates in some EMD cases, the overall survival to hospital discharge remains very low, indicating that its routine use in asystole and EMD lacks sufficient evidence to support its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcium: limited indications, some danger. Thompson, BM., Steuven, HS., Tonsfeldt, DJ., et al.[2013]

In a study of 111 patients with severe hyperkalemia, intravenous calcium gluconate was found to significantly improve main rhythm disorders on ECG, indicating its potential effectiveness in treating critical heart rhythm issues caused by high potassium levels.

However, the treatment did not show significant effects on non-rhythm ECG disorders, suggesting that calcium gluconate may be specifically beneficial for certain types of cardiac complications associated with hyperkalemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of calcium gluconate in the treatment of hyperkalemia. Celebi Yamanoglu, NG., Yamanoglu, A.[2022]

Low-calcium hemodialysis (LCHD) effectively reduced serum calcium levels in patients with hypercalcemic crisis, with an average decline of 4.63 mg/dL observed in a study of 42 patients, most of whom had malignancies.

Refractory cases, which did not respond to treatment, had significantly higher mortality rates (58.8%) compared to improved cases (10.5%), highlighting the urgency of prompt management in hypercalcemic crises.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of Low-Calcium Hemodialysis in the Treatment of Hypercalcemic Crisis. Trabulus, S., Oruc, M., Ozgun, E., et al.[2019]

The European Resuscitation Council and American Heart Association recommend a rapid administration of calcium chloride to protect the heart during hyperkalemia, but the formulations of calcium chloride can differ across European countries.

To reduce the risk of errors in treatment, the guidelines should specify calcium doses clearly in terms of mmol/L, mEq, or mg of calcium ions, ensuring consistency in administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The amount of calcium in calcium chloride - Is there a need to clarify emergency treatment of hyperkalaemia algorithm? Putowski, M., Jaskuła, J., Woroń, J.[2023]

In a study of 104 patients with out-of-hospital cardiac arrest and pulseless electrical activity (PEA), those who received calcium chloride had a lower rate of return of spontaneous circulation (20%) compared to those who received a placebo (39%), suggesting that calcium may not be beneficial in this context.

At 30 days post-arrest, only 2.2% of patients in the calcium group were alive compared to 13.6% in the placebo group, indicating potential harm from calcium administration rather than a therapeutic benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of calcium in patients with pulseless electrical activity and electrocardiographic characteristics potentially associated with hyperkalemia and ischemia-sub-study of the Calcium for Out-of-hospital Cardiac Arrest (COCA) trial. Vallentin, MF., Povlsen, AL., Granfeldt, A., et al.[2023]

In a study involving laboratory rats, verapamil hydrochloride was found to effectively reverse calcium-induced cardiac arrest, resulting in an impressive 83% survival rate compared to 0% in control groups.

Magnesium chloride did not demonstrate any efficacy in reversing cardiac arrest caused by high calcium levels, highlighting the potential of verapamil as a therapeutic option for hypercalcemic cardiac toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Verapamil reverses calcium cardiotoxicity. Zaloga, GP., Malcolm, D., Holaday, J., et al.[2019]

In a study involving 57 dogs undergoing cardiopulmonary bypass and one hour of global myocardial ischemia, an intracellular-like calcium-bearing solution (ICS) significantly improved heart function after ischemia compared to a calcium-free extracellular-like solution (ECS) and control solutions.

The ICS showed better postischemic ventricular performance regardless of how it was administered, indicating its potential as a more effective treatment for heart function recovery after ischemic events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An intracellular-like cardioplegic solution. Its enhancement of myocardial protection. Christlieb, IY., Clark, RE.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Calcium administration during cardiac arrest: a systematic review. [2018]

2. Ireland pubmed.ncbi.nlm.nih.gov

Effect of calcium vs. placebo on long-term outcomes in patients with out-of-hospital cardiac arrest. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Calcium: limited indications, some danger. [2013]

4. India pubmed.ncbi.nlm.nih.gov

The effect of calcium gluconate in the treatment of hyperkalemia. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

The Use of Low-Calcium Hemodialysis in the Treatment of Hypercalcemic Crisis. [2019]

6. Ireland pubmed.ncbi.nlm.nih.gov

The amount of calcium in calcium chloride - Is there a need to clarify emergency treatment of hyperkalaemia algorithm? [2023]

7. Ireland pubmed.ncbi.nlm.nih.gov

Effect of calcium in patients with pulseless electrical activity and electrocardiographic characteristics potentially associated with hyperkalemia and ischemia-sub-study of the Calcium for Out-of-hospital Cardiac Arrest (COCA) trial. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Verapamil reverses calcium cardiotoxicity. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

An intracellular-like cardioplegic solution. Its enhancement of myocardial protection. [2019]